1. Field of the Invention
This invention relates to the dispensing of pharmaceutical preparations. More particularly, the invention relates to an interactive drug dispenser, including a means for actively controlling the pattern in which doses of one or more pharmaceutical preparations are administered to a patient. The device further includes an improved means for therapeutic drug monitoring.
2. Description of Background Art
When a physician prescribes medication in a nonhospital setting or when an over-the-counter medication is sold, substantial reliance is placed on the patient to comply with the dosing instructions. Unfortunately, even in the case of acute illness, patient compliance with the prescribed dosing regimen is often casual or negligent. This can lead to misinterpretation by persons monitoring the patient's progress regarding the severity of the diseases, the effectiveness of the prescribed dose of drug, or the effectiveness of the drug itself, at any dose.
A number of devices have been proposed heretofore as aids to reliable self-medication. These include:
passive medication containers that segregate medicines according to the times they should be taken (for example, the dispensing packages in which birth control pills are marketed);
medication dispensers that provide clock-actuated alarms (see, for example, U.S. Pat. Nos. 3,651,984 to Redenbach and 4,419,016 to Zoltan);
medication dispensers from which the patient can receive medication only within certain time intervals (see, for example: U.S. Pat. Nos. 3,722,739 to Blumberg; 3,762,601 to McLaughlin; and 3,815,780 to Bauer);
medication dispensers designed for general use in therapeutics, lacking specifications peculiar to particular pharmaceuticals (see, for example, U.S. Pat. No. 3,911,856 to Ewing); and
medication dispensers that record the times at which the patient removes medication (see, for example: U.S. Pat. No. 4,034,757 to Glover; 4,360,125 to Martindale et al.; and 4,504,153 to Schollmeyer et al.).
Other references relating to this general subject include the following: U.S. Pat. Nos. 3,369,697 to Glucksman et al.; 3,395,829 to Cogdell et al.; 3,917,045 to Williams; 3,968,900 to Stambuk; 3,998,356 to Christensen; 4,207,992 to Brown; 4,223,801 to Carlson; 4,258,354 to Carmon et al.; 4,275,384 to Hicks et al.; 4,361,408 to Wirtschafter; 4,367,955 to Ballew; 4,382,688 to Machamer; 4,448,541 to Wirtschafter; 4,473,884 to Behl; 4,483,626 to Noble; 4,490,711 to Johnston; and 4,526,474 to Simon.
These prior art devices are sometimes helpful aids for improving the reliability of self-medication. However, implicit in these devices is the assumption that dosage regimen and patient condition are unchanging. In the reality of everyday therapeutics, however, both the prescription of drugs and the self-administration of drugs are subject to many contingencies, including, but not limited to:
changes in the course or nature of the patient's disease;
changes in the overall reliability with which the patient takes a given medication;
particular circumstances that may arise which will prevent the patient from faithfully following the prescribed regimen (e.g., having no access to water, being preoccupied by other business, having previously exhausted the medication supply, or being in a social situation where self-administration of drugs would be embarrassing);
changes in the patient's physiological mechanisms of drug absorption, distribution, metabolism or excretion that necessitate changes in the dosing regimen; and
the occurrence of acute nausea or vomiting that precludes the oral self-administration of a particular medication.
The present application is a continuation-in-part of U.S. patent application Ser. No. 899,412, filed Aug. 22, 1986, incorporated herein by reference. That application is directed to a contingent dosing device which is capable of directing in an interactive or contingent manner the dispensing of a sequence of pharmaceutical doses to a patient. The present invention relates to an improved method of therapeutic drug monitoring, and in a preferred embodiment is essentially an improvement of the contingent dosing device disclosed in the parent application hereto.
Therapeutic drug monitoring (TDM) refers to the practice of measuring the concentration of drug in a patient's plasma (or other biological fluid, e.g. saliva, urine, tear film, etc.) so as to select the dosage regimen of the drug that will maintain drug concentrations within the therapeutically optimum range. Typically, drugs subject to TDM have generally recognized upper and lower limits for drug concentration in plasma, so that optimization of the dosage regimen will maintain the drug concentration within those limits. Pharmacokinetic information on the drug in question can indicate to the prescribing physician how much to adjust the dosage regimen in order to bring suboptimal drug concentration into the optimal range. There are currently a number of drugs which are frequently monitored with commercial assays, and as clinical pharmacology progresses in its understanding of drugs, it is certainly foreseeable that more drugs will become the subject of TDM.
Proper interpretation of TDM values by a physician requires first of all a sensitive, specific and precise assay, so that the measured value accurately reflects the true concentration of the drug in the patient's plasma (or other fluid). However, even where a sufficiently sensitive and specific assay is available, there is a further problem in interpretation to which the present invention is specifically directed. This problem is that the proper interpretation of the measured concentration value strongly depends upon the patient's having accurately followed the prescribed dosing regimen in the days prior to the taking of the blood sample for TDM. If the patient has failed to do so, the drug concentration value will deviate from that which would be expected with proper dosing, and the doctor's decision regarding the need for dose adjustment may be based on a mistaken assumption as to the patient's having properly followed the prescribed dosing regimen. Or, if the doctor does not recognize that the patient has followed an incorrect regimen, his other decision to adjust the dose may be based on an incorrect assumption about the size and timing of doses actually taken by the patient. Thus, there are three quite different bases for a suboptimal TDM test result: (1) the incorrect dosing regimen taken correctly; (2) the correct dosing regimen taken incorrectly; or (3) the incorrect dosing regimen taken incorrectly. Further, those skilled in the art will recognize that certain combinations of this third possibility may result in an optimal TDM test result, though such result is a false basis for concluding that the patient is receiving optimal therapy, inasmuch as poor compliance with prescribed drug regimens is often inconsistent and irreproducible, day to day.